Intravenous drug users (IVDUs) are one of the at-risk subpopulations for HIV-1 infection and the subsequent development of AIDS. Variable rates and forms of the HIV-1 related disease progression have been noted, with IVDUs experiencing a particularly poor prognosis. Nutritional deficiencies result in immune dysregulation and multiple end organ damage in many clinical settings, including HIV-1 infection. Since IVDUs are at high risk for nutritional deficiencies, these alterations may contribute to the increased morbidity and mortality observed in HIV-1 infected IVDUs. The principal hypothesis of the proposed investigation is that nutritional deficiencies are associated with accelerated immune dysregulation and disease progression and thereby contribute to the increased morbidity and mortality observed in HIV-1 infected IVDUs. The proposed project represents collaboration between uniquely qualified groups of investigators already working in all of the areas proposed here. The study population for this project will consist of 75 HIV-1 seropositive and 75 HIV-1 seronegative IVDUs recruited by random assignment from available cohorts using a "gentreat" program. Both groups of participants will be elevated at 6-month intervals to characterize progressive nutritional changes as they relate to immune function and to health outcomes. Determination of nutritional status will include (1) biochemical markers of both overall nutritional and specific nutrient status (2) dietary history, (3) anthropometry, and (4) clinical nutrition examination. The influence of nutritional status upon HIV-1 disease progression in IVDUs will be assessed by monitoring its impact upon the following dependent variables: (a) immunological parameters (immune cell subpopulations, functional assays of immunity, levels of immunoglobulins), (b) disease progression (beta2- microglobulin, CD4 cell number neopterin) (c) morbidity (incidence of opportunistic infections/malignancies, neurological complications, number and length of hospitalizations, disease state) and (d) mortality. Multiple independent variables will also be considered in the analyses including: (a) nutritional status, (b) drug using behavior (frequency and types of drugs injected, quantities used, needle-sharing behavior) (c) sexual history, and (d) medical history (including history of alcohol and other drugs not used intravenously). Nutritional abnormalities have been documented in early HIV-1 infection, and are a hallmark characteristic of AIDS. The nutritional status of IVDUs is suspected to be inadequate, particularly in the setting of HIV-1 infection. As nutritional factors may contribute to the very high rates of morbidity and mortality among this group of HIV-1 infected patients, substantive data are currently required to develop methods and to institute appropriate means of nutritional support in this expanding group of patients. The present project will permit us to determine the relationships between nutritional status, drug addiction and the development of HIV-1 disease progression in IVDUs.